CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure.

BACKGROUND: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually. Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery. An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced. While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising. METHODS/DESIGN: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support. Following assent from a relative, adults (18-65 years) with severe, but potentially reversible, respiratory failure (Murray score >/= 3.0 or hypercapnea with pH < 7.2) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment. The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables. Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial. 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test). Secondary outcomes include patient morbidity and health status at 6 months. DISCUSSION: Analysis will be based on intention to treat. A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments.

Poly-methyl pentene oxygenators have improved gas exchange capability and reduced transfusion requirements in adult extracorporeal membrane oxygenation.

The performance of poly-methyl pentene (PMP) oxygenators (Medos Hilite 7000LT) was compared with that of silicone membrane (SM) oxygenators (Medtronic 1-4500-2A) for adult extracorporeal membrane oxygenation (ECMO). Forty consecutive patients were selected retrospectively pre- and post-introduction of PMP oxygenators. They were selected according to the dates they received ECMO and were separated into two equal groups with similar backgrounds. The flow path resistance, gas and heat exchange efficiency, consumption of coagulation factors and platelets, blood transfusion requirements, and incidence of clots for each oxygenator type was assessed. Adult PMP oxygenators showed lower blood path resistance than SM oxygenators. However, lower consumption of blood products in these oxygenators was a direct result of their smaller surface area and heparin coated design, reducing contact activation of coagulation factors. These oxygenators are noticeably smaller, require lower priming volumes, and have better gas exchange capability than SM oxygenators. They showed greater stability and preservation of coagulation factors and platelets compared with SM oxygenators. They also had the advantage of a functioning integrated heat exchanger. Using a single PMP oxygenator in the first instance may be adequate for the majority of patients and would significantly reduce red blood cell consumption during ECMO.

Extracorporeal life support in pertussis.

Severe B. pertussis infection in infants is characterized by severe respiratory failure, pulmonary hypertension, leukocytosis, and death. This retrospective case analysis highlights the course and outcome of severe B. pertussis infection treated with extracorporeal membrane oxygenation (ECMO) at a single center. Over the last decade, out of a total caseload of nearly 800 infants and children, 12 infants with severe B. pertussis have been referred for ECMO therapy to our center. All infants with pertussis infection who received ECMO therapy were less than 3 months of age at presentation and unvaccinated. There was a high mortality rate (7 of 12 infants died), which was associated with an elevated neutrophil count at presentation and multiorgan dysfunction characterized by intractable pulmonary hypertension, persistent systemic hypotension, renal insufficiency, and fits. ECMO should be offered to children with pertussis infection and respiratory failure refractory to mechanical ventilation. However, further research is required to determine the optimal management for infants receiving ECMO therapy with this disease.

Extracorporeal membrane oxygenation for chickenpox pneumonia: a single institution's experience.

The experience of extracorporeal membrane oxygenation (ECMO) use for severe chickenpox pneumonia was reviewed. Case notes of all patients treated with ECMO for this disease between 1992 and 1997 were reviewed. Of 405 patients referred for ECMO during this period, the diagnosis was chickenpox pneumonia in 14 (3.5%); all 14 were treated with ECMO. The median age of patients was 32.5 years (range 5 to 61 years). The median duration of extracorporeal support was 164 hours (range 45 to 652). Ten of 14 patients (71%) required hemofiltration. Overall survival of patients supported with ECMO was 57% (8 of 14). Deaths were caused by sepsis (5 patients, source identified in 4) and multiorgan failure (1 patient). Pneumonia as a complication of chickenpox can rapidly become severe and life threatening. Extracorporeal respiratory support may be helpful in patients refractory to conventional ventilation.

Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support.

Silicone oxygenators are the standard devices used for Extracorporeal Life Support (ECLS), but they have some limitations. Microporous polypropylene hollow fiber oxygenators overcome many of these problems but, unfortunately, develop plasma leak. Polymethyl-pentene (PMP) is a novel oxygenator material. We report our initial experience with the Medos Hilite 7000LT, a PMP hollow fiber oxygenator, in six adult respiratory ECLS patients with these characteristics: age, mean 32.2 (+/-13) years; weight, mean 81.2 (+/-17) kg; PaO2/FIO2, mean 62.8 [+/-33] mm Hg; Murray Score, mean 3.4 [+/-0.3]; and sepsis related organ failure assessment score, mean 9.6 [+/-2.3]. One patient was cannulated within 10 hours of multiple trauma and 1 hour after thoracolaparotomy; another patient was cannulated 12 hours after a thoracotomy. All six patients survived. Heparin was infused (7.8-32.5 u/kg/hr) to maintain activated clotting time at 162 to 238 seconds; international normalized ratio was 0.9 to 3.4. Two of the six patients required transfusions of fresh frozen plasma, receiving one and five units, respectively. Fibrinogen was 1.4 to 6 g/dl; no cryoprecipitate was needed. Platelet counts were between 65 and 306, and very little platelet transfusion (mean 2.33; +/-3.03 units per patient) was required to maintain these levels. Two patients did not require any platelet transfusion. Maximum blood flow was 5.3 L/min, sweep was 3 to 10 L/min, and resistance was 11 to 43 Paul Wood Units. There were no oxygenator failures. Mean duration of ECLS was 151.7 hours (+/-75.6). Our initial experience with PMP oxygenators in adults was satisfactory, and platelet consumption and resistance to blood flow seem to be greatly reduced with PMP.

How does the changing profile of infants who are referred for extracorporeal membrane oxygenation affect their overall respiratory outcome?

OBJECTIVE: Extracorporeal membrane oxygenation has been shown to be effective in term neonates with severe but reversible lung disease within the context of randomized, controlled trials. Extracorporeal membrane oxygenation now has been open to a wider population of infants in the United Kingdom, and other treatments have become available. The population referred for extracorporeal membrane oxygenation, therefore, has changed. The aims of this study were to (1) compare respiratory outcomes of infants who received extracorporeal membrane oxygenation in recent years with those from 10 years ago and (2) determine whether respiratory outcome varied with diagnostic group. METHODS: All infants who were referred to a single extracorporeal membrane oxygenation center and were <12 months old during a 7-year period were eligible. One year after extracorporeal membrane oxygenation, lung volume, airway conductance, maximum expiratory flow, and indices of tidal breathing were measured. RESULTS: A total of 106 infants (77% of those eligible) were tested, and results were compared with those of 51 infants referred for extracorporeal membrane oxygenation as part of the original United Kingdom extracorporeal membrane oxygenation trial. Lung volume was not different, but there was a strong trend for the infants who were seen in more recent years to have better forced expiratory flow and specific airway conductance. Restricting analysis to the major subgroup (meconium aspiration) confirmed these findings. When divided into diagnostic subgroups, infants who required extracorporeal membrane oxygenation for respiratory distress syndrome or who were >2 weeks old when extracorporeal membrane oxygenation was commenced had a poorer respiratory outcome than others. CONCLUSIONS: The respiratory outcome of infants who were treated beyond the tightly regulated criteria of the United Kingdom trial remains good and even shows a trend toward improvement. Certain subgroups require extracorporeal membrane oxygenation for longer and have poorer pulmonary function when followed up.

A comparison of radiographic signs of pulmonary inflammation during ECMO between silicon and poly-methyl pentene oxygenators.

INTRODUCTION: The inflammatory response caused by extracorporeal membrane oxygenation (ECMO) is clearly visible within the first 24 h of cannulation. The inflammatory process affects all areas of the lung, even areas previously spared by the primary disease. OBJECTIVE: To compare the change in the radiographic signs of inflammatory response to ECMO between poly-methyl pentene and silicon oxygenators. STUDY DESIGN: Retrospective review of neonates and adults pre- and post-replacement of silicon oxygenators with poly-methyl pentene devices. Data were collected from Extracorporeal Life Support Organisation (ELSO) registry forms and patient records. Results were analysed by quantitative and semi-quantitative methods. RESULTS: There was a significant reduction in the radiographic signs of inflammatory response to ECMO, and a reduction in the time taken to revert to pre-ECMO state in the neonatal poly-methyl pentene group compared to silicon. However, there was no significant reduction in the duration of ECMO runs and the percentage survival between these groups in the neonates. In adults, there was no difference in severity of radiographic signs between groups. However, the inflammatory changes were relatively delayed in the adult poly-methyl pentene group. CONCLUSION: Polymethyl pentene (Medos) oxygenators have reduced the host's response phenomenon 'white out' in neonates, and caused a delayed response in adults. This is most likely a consequence of smaller blood contact surface area combined with the effect of heparin coating of the oxygenator membrane. However, recovery was not a function of the type of gas exchange device used.

A potential propensity for failure secondary to clot embolism in neonatal ECMO.

OBJECTIVE: To report a single case of oxygenator failure caused by clot embolism originating from the bladder; and to discuss some preventative options. CASE REPORT: A 2.5 kg neonate with a diagnosis of influenza A received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) for cardiorespiratory support. Halfway through treatment, she underwent an elective circuit change for numerous clots in her circuit. The patient continued to consume vast quantities of platelets and developed a fatal oxygenator failure after 18 days. DISCUSSION: Amongst the factors influencing the outcome in events of a sudden unexpected oxygenator failure are the severity of patient illness, the size of the clot relative to the size of the oxygenator, the availability of a previously primed circuit and the ease and speed of priming a new oxygenator. CONCLUSION: There is a need for improvement in the design of small oxygenators and ECMO circuits. Adjustment of the coagulation parameters and lowering the tolerance towards clots in the circuit by electively changing them may reduce the incidence of sudden unexpected oxygenator failure. However, using a slightly larger Medos oxygenator may gain valuable time needed to arrange an oxygenator/circuit change.

Performance of polymethyl pentene oxygenators for neonatal extracorporeal membrane oxygenation: a comparison with silicone membrane oxygenators.

OBJECTIVE: To review the performance of polymethyl pentene versus silicone oxygenators in terms of efficiency in priming and oxygenation, oxygenator resistance, requirements for coagulation proteins and consumption of blood products, for neonatal extracorporeal membrane oxygenation (ECMO) patients. STUDY DESIGN: Forty consecutive neonates were selected retrospectively pre- and post-introduction of the new polymethyl pentene (PMP) oxygenators. They formed two equal groups. After calculation of the sample size, data were collected from ELSO registry forms and patient records. Results were analysed using parametric and non-parametric tests. RESULTS: Neonatal PMP (N-PMP) oxygenators were smaller, faster and easier to prime. They were less efficient than silicone oxygenators, especially in carbon dioxide elimination, and, therefore, required higher sweeps. The preservation of coagulation proteins was significantly better, but there was no reduction in the consumption of blood products, despite having less than half the surface area and significantly lower blood path resistance. CONCLUSION: Small PMP oxygenators (Medos Hilite 800 LT) provide adequate gas exchange and offer technical advantages in terms of more efficient priming, reduced haemodynamic resistance and better control and preservation of coagulation proteins than silicone oxygenators.

An in vitro method for comparing biocompatibility of materials for extracorporeal circulation.

UNLABELLED: We measured the response of fresh heparinized human blood to recirculation through circuits made of LVA (Portex Industries, Hythe, Kent, UK), SRT (Rehau UK, Langley, Slough, UK) and Tygon S-65-HL (Norton Performance Plastics, Corby, Northants, UK), as control. Circuit construction: 1/2 in. tubing, heat exchanger (Dideco D-720P), Stockert roller pump, just underoccluded, Cincinnati Sub Zero heater, circuit volume of 500 ml. Flow 3.45 l/min, 37 degrees C. SAMPLES: at 10 min, 1, 2, 4 and 6 h. n=5 in each group; 2/5 SRT experiments were stopped at 45 and 60 min due to overpressurization. RESULTS: Baseline activated clotting time (ACT) of 300 s, increasing in all groups as fibrinogen fell to zero with SRT and LVA. Minimum fibrinogen was 1 g/l for Tygon. Absolute thrombocytopenia occurred (SRT and LVA 60 min and Tygon 240 min). International normalized ratio (INR) in both the SRT and LVA circuits increased, but mean increase for Tygon (0.56) was smaller than the other two materials. Plasma free haemoglobin increased in all three materials; the increase was greater in the LVA circuits compared to the control. C5b9 levels increased equally in all groups. Lactoferrin levels rose equally in all groups to a maximum at 150 min. The neutrophil counts fell, mirroring the lactoferrin. The total white cell counts also fell in all groups; in the LVA circuits, the fall was significantly lower than in the control. Rapid disappearance of platelets and fibrinogen from the blood in the SRT and LVA circuits excludes them both from extracorporeal use. Paradoxically, SRT caused the least complement activation of the three materials. This method can be used to compare biocompatibility.

A pilot investigation of mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO).

OBJECTIVE: To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured. RESULTS: No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions. CONCLUSIONS: Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.